The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Read our disclaimer for details.

Tumor control rate is defined as the sum of objective response rate (CR+PR) and stable disease (SD) rate.

Original Secondary Outcome Measures ICMJE (submitted: June 9, 2010)

Antitumor Activity of RO4929097 [ Time Frame: End of Study (Anticipated June 2011) ]

To assess the antitumor activity of RO4929097 through secondary endpoints including: duration of radiologic response, rate of disease stabilization, rate of tumor control rate (CR+PR+SD) and progression-free and overall survival rates

Safety and Tolerability of RO4929097 [ Time Frame: End of Study (Anticipated June 2011) ]

To assess the safety and tolerability of single agent RO4929097 in patients with advanced RCC

Notch Biomarker Expression [ Time Frame: End of Study (Anticipated June 2011) ]

To explore expression of Notch biomarkers in RCC patients and their potential interaction with RO4929097 response and toxicity.

Patients receive gamma-secretase/Notch signalling pathway inhibitor RO4929097 PO on days 1-3, 8-10, and 15-17. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Interventions:

Drug: Gamma-Secretase Inhibitor RO4929097

Other: Laboratory Biomarker Analysis

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ICMJE

Completed

Actual Enrollment ICMJE (submitted: January 19, 2017)

12

Original Estimated Enrollment ICMJE (submitted: June 9, 2010)

39

Actual Study Completion Date

December 2013

Actual Primary Completion Date

May 2012 (Final data collection date for primary outcome measure)

Eligibility Criteria ICMJE

Inclusion Criteria:

Patients must have histologically or cytologically confirmed predominant clear cell, renal cell carcinoma, NOS, that is recurrent or metastatic

Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as >= 20 mm with conventional techniques or as >= 10 mm with spiral CT scan; scans must be completed within 4 weeks prior to starting study treatment

Patients must have had one prior therapy for non-resectable renal cell carcinoma with a VEGF/VEGFR targeted therapy (e.g. sunitinib, sorafenib, other VEGFR tyrosine kinase inhibitor, or bevacizumab)

Patients must be able to take oral medication and have no evidence of bowel obstruction

The effects of RO4929097 on the developing human fetus at the recommended therapeutic dose are unknown; for this reason and because Notch signal pathway inhibitors are known to be teratogenic, if women of childbearing potential do not abstain from sexual activity (documentation that they have been abstinent from sexual activity at least 4 weeks prior to study entry) they must use two forms of contraception (i.e., barrier contraception and one other method of contraception) at least 4 weeks prior to study entry; women of childbearing potential be can either be abstinent or use two forms of contraception for the duration of study participation, and be either abstinent or use two forms of contraception for at least 12 months post-treatment; men must use condoms when sexually active with women for the duration of study participation and at least 12 months post-treatment

Should a woman become pregnant or suspect she is pregnant while she or her partner are participating in this study and for 12 months after study participation, the patient should inform the treating physician immediately

Pregnancy Testing; women of childbearing potential are required to have a negative serum pregnancy test (with a sensitivity of at least 25 mIU/mL) within 10-14 days and within 24 hours prior to the first dose of RO4929097 (serum or urine); a pregnancy test (serum or urine) will be administered every 4 weeks if their menstrual cycles are regular or every 2 weeks if their cycles are irregular while on study within the 24-hour period prior to the administration of RO4929097; a positive urine test must be confirmed by a serum pregnancy test; prior to dispensing RO4929097, the investigator or clinical staff must confirm and document the patient's use of two contraceptive methods or abstinence, dates of negative pregnancy test, and confirm the patient's understanding of the teratogenic potential of RO4929097

Female patients of childbearing potential are defined as follows:

Patients with regular menses

Patients, after menarche with amenorrhea, irregular cycles, or using a contraceptive method that precludes withdrawal bleeding

Women who have had tubal ligation

Female patients may be considered to NOT be of childbearing potential for the following reasons:

The patient has undergone total abdominal hysterectomy with bilateral salpingo-oophorectomy or bilateral oophorectomy

The patient is medically confirmed to be menopausal (no menstrual period) for 24 consecutive months

Pre-pubertal females; the parent or guardian of young female patients who have not yet started menstruation should verify that menstruation has not begun; if a young female patient reaches menarche during the study, then she is to be considered as a woman of childbearing potential from that time forward

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Patients must not have had major surgery, chemotherapy, or radiation therapy within 4 weeks of starting the study treatment (6 weeks for nitrosoureas or mitomycin C); prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that had not been irradiated; patients must have recovered from the toxic effects from any prior therapy to =< grade 1, except alopecia

Patients may not be receiving any other investigational agents concurrently

Patients with controlled brain metastases (no radiographic progression following radiation and/or surgical treatment and no neurological signs or symptoms) that are clinically and radiologically stable for at least 6 months will be allowed but must NOT be currently taking corticosteroids (e.g. dexamethasone) to control neurologic symptoms of brain metastases

Patients with unstable or symptomatic brain metastases, spinal core compression, or carcinomatosis meningitis, or evidence of brain or leptomeningeal disease on screening CT or MRI scan are excluded

History of allergic reactions attributed to compounds of similar chemical or biologic composition to RO4929097 or other agents used in the study

Patients taking medications with narrow therapeutic indices that are metabolized by cytochrome P450 (CYP450), including warfarin sodium (Coumadin®) are ineligible

Preclinical studies indicate that RO4929097 is a substrate of CYP3A4 and inducer of CYP3A4 enzyme activity; caution should be exercised when dosing RO4929097 concurrently with CYP3A4 substrates, inducers, and/or inhibitors; furthermore, patients who are taking concurrent medications that are strong inducers/inhibitors or substrates of CYP3A4 should be switched to alternative medications to minimize any potential risk; if such patients cannot be switched to alternative medications, they will be ineligible to participate in this study

Patients with malabsorption syndrome or other condition that would interfere with intestinal absorption; patients must be able to swallow tablets

Patients who are serologically positive for Hepatitis A, B or C, or have a history of liver disease, other forms of hepatitis or cirrhosis are ineligible

Patients with uncontrolled hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia or hypokalemia defined as less than the lower limit of normal for the institution, despite adequate electrolyte supplementation are excluded from this study

Pregnant women are excluded from this study because RO4929097 is a Notch pathway-inhibiting agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with RO4929097, breastfeeding should be discontinued if the mother is treated with RO4929097; these potential risks may also apply to other agents used in this study

Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with RO4929097; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated